Arterial ischemic stroke (AIS) is a common and devastating disorder of childhood. In spite of this, there is little evidence regarding etiology or outcomes with which to inform treatment. This proposal aims to support the early career development of an academic pediatric neurologist focusing upon the investigation of prognostic factors in childhood-onset AIS. Specifically, we are investigating the role of stroke subtype and biomarkers upon the risk of recurrent stroke. Preliminary results suggest that acutely elevated biomarkers of hypercoagulability are likely associated with specific subtypes in childhood-onset AIS. Further, these biomarkers may be prognostic or recurrent AIS and/or adverse neurological outcome. Certain stroke subtypes, such as arteriopathy, are also associated with recurrent AIS. Therefore, we seek to explore the combined prognostic significance of subtype and biomarkers of hypercoagulability upon recurrent AIS in children with stroke. To that end, our initial aim is to confirm the reliability of a consensus based classification system in childhood- onset AIS. This analysis will be performed as an ancillary study of an established NIH database of over 100 consecutively enrolled patients with childhood-onset AIS. In a separate, four-center cohort of prospectively enrolled children with childhood onset AIS, we will evaluate the relationship between stroke subtype and acutely elevated biomarkers of hypercoagulability. Finally, we will evaluate the prognostic significance of biomarkers of hypercoagulability, stroke subtype, and systemic inflammation for recurrent cerebrovascular events in childhood-onset AIS. PUBLIC HEALTH RELEVANCE: Childhood stroke is a poorly understood disease. The most prevalent risk factors identified to date include stroke subtype and coagulation abnormalities. The systematic collection of the proposed biomarkers may provide insight into 1) the pathophysiology of childhood stroke, 2) the prediction of recurrent stroke, and 3) the identification of patients who need more aggressive therapies.